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Gary Kaufman

Bio: Gary Kaufman is an academic researcher from Boston University. The author has contributed to research in topics: Low birth weight & Birth weight. The author has an hindex of 4, co-authored 4 publications receiving 724 citations.

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Journal ArticleDOI
09 Jan 2002-JAMA
TL;DR: In this study, maternal CYP1A1 and GSTT1 genotypes modified the association between maternal cigarette smoking and infant birth weight, suggesting an interaction between metabolic genes and cigarette smoking.
Abstract: ContextLittle is known about genetic susceptibility to cigarette smoke in relation to adverse pregnancy outcomes.ObjectiveTo investigate whether the association between maternal cigarette smoking and infant birth weight differs by polymorphisms of 2 maternal metabolic genes: CYP1A1 and GSTT1.Design, Setting, and ParticipantsCase-control study conducted in 1998-2000 among 741 mothers (174 ever smokers and 567 never smokers) who delivered singleton live births at Boston Medical Center. A total of 207 cases were preterm or low-birth-weight infants and 534 were non–low-birth-weight, full-term infants (control).Main Outcome MeasureBirth weight, gestation, fetal growth by smoking status and CYP1A1 MspI (AA vs Aa and aa, where Aa and aa were combined because of small numbers of aa and similar results), and GSTT1 (present vs absent) genotypes.ResultsWithout consideration of genotype, continuous maternal smoking during pregnancy was associated with a mean reduction of 377 g (SE, 89 g) in birth weight (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.7). When CYP1A1 genotype was considered, the estimated reduction in birth weight was 252 g (SE, 111 g) for the AA genotype group (n = 75; OR, 1.3; 95% CI, 0.6-2.6), but was 520 g (SE, 124 g) for the Aa/aa genotype group (n = 43 for Aa, n = 6 for aa; OR, 3.2; 95% CI, 1.6-6.4). When GSTT1 genotype was considered, the estimated reduction in birth weight was 285 g (SE, 99 g) (OR, 1.7; 95% CI, 0.9-3.2) and 642 g (SE, 154 g) (OR, 3.5; 95% CI, 1.5-8.3) for the present and absent genotype groups, respectively. When both CYP1A1 and GSTT1 genotypes were considered, the greatest reduction in birth weight was found among smoking mothers with the CYP1A1 Aa/aa and GSTT1 absent genotypes (−1285 g; SE, 234 g; P<.001). Among never smokers, genotype did not independently confer an adverse effect. A similar pattern emerged in analyses stratified by maternal ethnicity and in analyses for gestation.ConclusionsIn our study, maternal CYP1A1 and GSTT1 genotypes modified the association between maternal cigarette smoking and infant birth weight, suggesting an interaction between metabolic genes and cigarette smoking.

579 citations

Journal ArticleDOI
TL;DR: In extremely premature infants, use of indomethacin during the first 48 hours of life was associated with a reduced need for PDA ligation, but an increased risk of NEC with intestinal perforation.
Abstract: Survival of extremely premature infants (< 27 weeks' gestational age) has improved over the past two decades. Indomethacin prophylaxis was used in these infants, who have the highest mortality and morbidity rates, to reduce the incidence of intraventricular hemorrhage and patent ductus arteriosus (PDA). Medical records of 65 extremely premature infants born at our institution between 1995 and 2001 were reviewed retrospectively to determine whether treatment of PDA with indomethacin in the first 48 hours of life reduces the need for PDA ligation or increases neonatal morbidity, when compared to treatment begun later. Thirty infants in the early treatment group (ETG) were treated during the first 48 hours after birth, and 32 infants in the standard treatment group (STG) were managed expectantly for PDA. Three infants died in the first hours of life and were eliminated from further analysis. ETG infants were 24.9 +/- 1.1 (mean +/- SD) weeks' gestation with a birth weight of 678 +/- 143 g. STG infants were 25.3 +/- 1.1 weeks (NS) and 730 +/- 125 g (NS). Hemodynamically significant PDA was diagnosed or confirmed by echocardiography in 19 ETG patients and 17 STG patients. Of the patients with hemodynamically significant PDA, 1 (5%) ETG patient and 6 (35%) STG patients underwent surgical ligation (p = 0.033). Necrotizing enterocolitis (NEC) with intestinal perforation was the most serious morbidity and occurred in 20% of infants in the ETG, but in no STG infant (p = 0.011). Four of the six infants in the ETG with NEC and intestinal perforation died. The overall mortality rate for all infants studied was 28%. We conclude that in extremely premature infants, use of indomethacin during the first 48 hours of life was associated with a reduced need for PDA ligation, but an increased risk of NEC with intestinal perforation.

81 citations

Journal ArticleDOI
TL;DR: The major environmental, nutritional and social factors as well as clinical variables known or suspected to be associated with PTD will be used to test for gene-environment interactions and to improve understanding of genetic influences on PTD and gene- Environment interactions.
Abstract: Preterm delivery (PTD) appears to be a complex trait determined by both genetic and environmental factors. Few studies have examined genetic influence on PTD. The overall goal of our study is to examine major candidate genes of PTD and to test gene–environment interactions. Our study includes 500 preterm trios, including 500 preterm babies and their parents and 500 maternal age-matched term controls. We will perform the transmission/disequilibrium test (TDT) on candidate genes thought to be important in each of the four biological pathways of PTD: (1) decidual chorioamionotic inflammation: interleukin 1 (IL-1), IL-6, and tumour necrosis factor (TNF); (2) maternal and fetal stress: corticotropin-releasing hormone (CRH); (3) uteroplacental vascular lesions: methylenetereahydrofolate reductase (MTHFR); and (4) susceptibility to environmental toxins: GSTM1, GSTT1, CYP1A1, CYP2D6, CYP2E1, NAT2, NQO1, ALDH2, and EPHX. We will also perform standard case-control analyses on the 500 preterm cases and 500 term controls to examine gene–environment interactions. The major environmental, nutritional and social factors as well as clinical variables known or suspected to be associated with PTD will be used to test for gene–environment interactions. This study integrates epidemiological and clinical data as well as genetic markers along major pathogenic pathways of PTD. The findings from this study should improve our understanding of genetic influences on PTD and gene–environment interactions.

59 citations

Journal ArticleDOI
TL;DR: Maternal genotypes for enzymes participating in metabolism of polycyclic aromatic hydrocarbons alter the association between cigarette smoking and birth weight, and this finding raises the question of whether metabolic genes interact with smoking.
Abstract: This study sought to clarify the relation, if any, between genetic susceptibility to cigarette smoke and adverse pregnancy outcomes. The working hypothesis was that the risk of reduced birth weight (or increased risk of low birth weight [LBW], <2500 g) is modified by maternal genetic susceptibility as defined by polymorphisms for two genes regulating the metabolism of polycyclic aromatic hydrocarbons, the most important carcinogens in tobacco smoke. A case-control study enlisted 741 women delivering live singleton infants, 567 had never smoked, whereas 174 had smoked at some time. The series included 207 preterm or LBW infants. All three possible genotypes for the CYP1A1 Mspl polymorphism (AA, homozygous wild type; Aa, heterozygous variant type; aa, homozygous variant type) were analyzed, as was the presence or absence of the GSTT1 deletion polymorphism. The mean birth weight in women who had smoked at some time in their lives was 280 g lower than for those who had never smoked, and the mean gestational age was 0.8 week shorter. The odds ratio (OR) for preterm birth was 1.8 in the smokers. Continuous smoking during pregnancy carried an OR for LBW of 2.1; the mean birth weight was reduced by 377 g compared with nonsmokers. When analyzing CYP1A1, the reduction in birth weight was 252 g for the AA genotype (OR, 1.3) and 520 g for the Aalaa genotype group (OR, 3.2). Birth weight was reduced by 285 g (OR, 1.7) when the GSTT1 was present and 642 g (OR, 3.5) when it was absent. Birth weights were most reduced, by a mean of 1285 g, in smoking mothers bearing the CYP1A1 Aalaa and GSTT1 absent genotypes. Similar effects were noted for gestational age. Genotype had no independent adverse effect on women who had never smoked. Comparable results emerged when allowing for maternal ethnicity. Maternal genotypes for enzymes participating in metabolism of polycyclic aromatic hydrocarbons alter the association between cigarette smoking and birth weight. This finding raises the question of whether metabolic genes interact with smoking, and it may in time help to identify high-risk women who might be persuaded not to smoke.

39 citations


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Journal ArticleDOI
TL;DR: A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.

6,275 citations

Journal ArticleDOI
TL;DR: This review focuses on those experimental studies that have investigated the critical windows during which perturbations of the intrauterine environment have major effects, the nature of the epigenetic, structural, and functional adaptive responses which result in a permanent programming of cardiovascular and metabolic function, and the role of the interaction between the pre- and postnatal environment in determining final health outcomes.
Abstract: The "fetal" or "early" origins of adult disease hypothesis was originally put forward by David Barker and colleagues and stated that environmental factors, particularly nutrition, act in early life to program the risks for adverse health outcomes in adult life. This hypothesis has been supported by a worldwide series of epidemiological studies that have provided evidence for the association between the perturbation of the early nutritional environment and the major risk factors (hypertension, insulin resistance, and obesity) for cardiovascular disease, diabetes, and the metabolic syndrome in adult life. It is also clear from experimental studies that a range of molecular, cellular, metabolic, neuroendocrine, and physiological adaptations to changes in the early nutritional environment result in a permanent alteration of the developmental pattern of cellular proliferation and differentiation in key tissue and organ systems that result in pathological consequences in adult life. This review focuses on those experimental studies that have investigated the critical windows during which perturbations of the intrauterine environment have major effects, the nature of the epigenetic, structural, and functional adaptive responses which result in a permanent programming of cardiovascular and metabolic function, and the role of the interaction between the pre- and postnatal environment in determining final health outcomes.

1,814 citations

Journal ArticleDOI
TL;DR: Clinical practice guidelines for congenital adrenal hyperplasia (CAH) recommend universal newborn screening for severe steroid 21-hydroxylase deficiency followed by confirmatory tests and recommend judicious use of medication during pregnancy and in symptomatic patients with nonclassic CAH.
Abstract: Objective: We developed clinical practice guidelines for congenital adrenal hyperplasia (CAH). Participants: The Task Force included a chair, selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), ten additional clinicians experienced in treating CAH, a methodologist, and a medical writer. Additional experts were also consulted. The authors received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society’s CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. Conclusions: We recommend universal newborn screening for severe steroid 21-hydroxylase deficiency followed by confirmatory tests. We recommend that prenatal treatment of CAH continue to be regarded as experimental. The diagnosis rests on clinical and hormonal data; genotyping is reserved for equivocal cases and genetic counseling. Glucocorticoid dosage should be minimized to avoid iatrogenic Cushing’s syndrome. Mineralocorticoids and, in infants, supplemental sodium are recommended in classic CAH patients. We recommend against the routine use of experimental therapies to promote growth and delay puberty; we suggest patients avoid adrenalectomy. Surgical guidelines emphasize early single-stage genital repair for severely virilized girls, performed by experienced surgeons. Clinicians should consider patients’ quality of life, consulting mental health professionals as appropriate. At the transition to adulthood, we recommend monitoring for potential complications of CAH. Finally, we recommend judicious use of medication during pregnancy and in symptomatic patients with nonclassic CAH.

1,114 citations

Journal ArticleDOI
TL;DR: Smoking during pregnancy is in many countries recognized as the most important preventable risk factor for an unsuccessful pregnancy outcome.
Abstract: The prevalence of smoking during pregnancy varies markedly across countries. In many industrialized countries, prevalence rates appear to have peaked and begun to decline, whereas in other countries smoking is becoming increasingly common among young women. Randomized controlled trials have shown that smoking interventions during pregnancy have had limited success. Smoking during pregnancy is in many countries recognized as the most important preventable risk factor for an unsuccessful pregnancy outcome. Smoking is causally associated with fetal growth restriction, and increasing evidence also suggests that smoking may cause stillbirth, preterm birth, placental abruption, and possibly also sudden infant death syndrome. Smoking during pregnancy also is generally associated with increased risks of spontaneous abortions, ectopic pregnancies, and placenta previa and may increase risks of behavioral disorders in childhood. Smoking during pregnancy will continue to be an important risk factor for maternal and fetal outcomes during pregnancy.

1,048 citations

Journal ArticleDOI
TL;DR: This review of research evidence on four varieties of gene-environment interplay considers epigenetic mechanisms by which environmental influences alter the effects of genes and focuses on variations in heritability according to environmental circumstances.
Abstract: Gene–environment interplay is a general term that covers several divergent concepts with different meanings and different implications. In this review, we evaluate research evidence on four varieties of gene–environment interplay. First, we consider epigenetic mechanisms by which environmental influences alter the effects of genes. Second, we focus on variations in heritability according to environmental circumstances. Third, we discuss what is known about gene–environment correlations. Finally, we assess concepts and findings on the interaction between specific identified genes and specific measured environmental risks. In order to provide an understanding of what may be involved in gene–environment interplay, we begin our presentation with a brief historical review of prevailing views about the role of genetic and environmental factors in the causation of mental disorders, and we provide a simplified account of some of the key features of how genes ‘work’. Over the past half-century there has been a series of changes in the generally prevailing views about the role of genetic and environmental factors in the causation of mental disorders. These changes were preceded in the first half of the 20th century (Cameron, 1956; Cairns, 1983; Kanner, 1959) by two background features. First, there was the introduction of unethical and abhorrent eugenic interventions on the misguided view of deterministic genetic effects (Devlin, Fienberg, Resnick, & Roeder, 1997). This background created a distrust of genetics in many behavioural scientists that has not entirely disappeared today despite genetic thinking and practice having changed completely (see Rutter, in press a). Second, there were numerous research reports of substantial associations between various environmental risk factors and the development of mental disorder. The Mental Hygiene movement placed great emphasis on the role of adverse experiences, both within and outside the family, in the predisposition to some mental disorders. This period also constituted the heyday of the influence of psychoanalysis on concepts and thinking in most of psychiatry and psychology. Behaviourism, led by the theorising of Pavlov and of Skinner, as well as by the advocacy of Watson, placed predominate emphasis on the power of learning with respect to all forms of behaviour. Within the field of child mental health, Bowlby’s (1951) review for the WHO of ‘maternal deprivation’, followed by Ainsworth’s (1962) reassessment a decade or so later, put forward a powerful case for the overwhelming influence of children’s upbringing in the early years. Reviews such as those by Pringle (1974) did much to popularise these views and foster

1,019 citations